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Transcript of Environmental Impacts on Reproductive Health: Foundations of the Science Association of Reproductive...
Environmental Impacts on Reproductive Health:Foundations of the Science
Association of Reproductive Health Professionalswww.arhp.org
Expert Medical Advisory Committee
• Kathleen Hill Besinque, PharmD, MSEd, FCSHP• Maureen Paul, MD, MPH• Barbara Sattler, RN, DrPH, FAAN• Ted Schettler, MD, MPH• Michael Thomas, MD (co-chair)• Tracey Woodruff, PhD, MPH (co-chair)• Sandy Worthington, MSN, WHNP-BC, CNM
Acknowledgment of Support
This project is funded through a grant from the Passport Foundation and the Richard and Rhoda Goldman Fund.
Faculty Disclosure
Speaker: Kirtly Jones, MD: nothing to disclose
• Note: Staff and committee disclosures listed in program
Learning Objectives
At the conclusion of this course, clinicians should be able to:• Appreciate impact of exposure to harmful
environmental chemicals and heavy metals on reproductive health
• Express value of incorporating basic questions about environmental risks into patient history & physical examination
more…
Learning Objectives (continued)
• Use resources that provide information about environmental exposures in their communities & patient populations
• Refer patients to relevant resources & further information to learn more about environmental risks
Awareness of Environmental Exposures & Impacts Is Growing
• Air pollution• Water contamination• Harmful substances in
physical structures and workplaces
• Food contamination• Personal care products
“…exposures of males and females to foreign substances prior to conception can affect both their ability to conceive and the health of their offspring.”
Davis DL, et al.JAMA. 1998
Awareness of Reproductive Effects Is Growing
Reproductive Trends in Some Geographic Areas Raise Concerns
• Increase in testicular cancer incidence• Decreasing sperm counts• Decline in serum testosterone• Earlier pubertal development in girls• Fewer males being born• Documented increases in certain types of
birth defects
Bray F, et al. Int J Cancer. 2006; Edmond LD, James LM. MMWR Surveill Summ. 1990; Euling et al. Pediatrics. 2008; Herman-Giddens ME. Int J Androl. 2006; Harris KB. Mol Genet Metab. 2007; Hertz-Picciotto et al. Environmental Health. 2008; Jørgensen N, et al. Int J Androl. 2006; Mackenzie CA. Environ Health Perspect. 2005; Travison TG, et al. J Clin Endocrinol Metab. 2007; Vu LT. J Pediatr. 2008.
Some Reproductive Effects Are Well Known
Jones HE, et al. Obstet Gynecol Clin North Am. 1998. EPA. 2008. Woodruff TJ, et al. Fertil Steril. 2008; CDC. 2009; US Surgeon General. 2005.
High exposure to: Can Increase the Risk of…
Tobacco smokeMiscarriageInfertilityPreterm delivery
Low semen qualityLow birth weightNeurodevelopmental abnormalities in offspring
Alcohol use Fetal alcohol syndromeMental retardation
Behavioral problemsBirth defects
Heavy metals (lead)MiscarriageInfertilityMenstrual irregularities
Abnormal spermAltered pubertal onset
Toluene (e.g., in paint thinner, solvents) Fetal solvent syndrome
DBCP (pesticide) Low sperm count Other male reproductive effects
Content Overview
This slide set will review:• State of the science• Windows of susceptibility• Patient counseling• Further information and resources
US Chemical Production and Importation Are High
GAO. 2006; EPA. 2008.
*Among those tested for certain properties, reproductive/environmental effects often have not been assessed.
87K 3K 8KApproximate no. of
chemicals registered for
commerce in US
are produced or imported in annual
quantities of >1 million pounds
--or one-tenth--have been tested for potential health
effects*
Reproductive health &fetal/child
development
Adapted from Hubbs-Tait et al. Psychological Science in the Public Interest. 2005.
Many Complex Factors Interact to Affect the Impact of Exposures
Exposure-Effect Continuum
CDC. 2009.
Biological uptake (exposure)
Target Organ Dose
Biologic Change/ Clinical Effect
Source
e.g., testis, ovary, transplacental transport
Breathing, eating/drinking, skin contact
e.g., air, water, food, soil
The Barker Hypothesis
Barker DJ. Trends Endocrinol Metab. 2002; Woodruff TK, Walker CL. Fertil Steril. 2008; Woodruff TJ, et al. Fertil Steril. 2008.
“Exposures to adverse insults during critical…windows of development can permanently reprogram normal physiologic responses, and thus give rise to…disorders later in life.”
Woodruff TJ, et al.Fertil Steril. 2008
Biomonitoring Can Yield Useful Information
• Measures chemical levels in body tissues or fluids (e.g., organ tissue, hair, breast milk, blood, urine)
• One way to document exposures• Often accurate at low levels• But…• Usually unable to identify source• Often clinical significance is unclear
Sexton K, et al. American Scientist. 2004.
Environmental Exposures and Critical Windows of Susceptibility
Woodruff TJ, et al. Fertil Steril. 2008.
Identified Reproductive Endpoints in Animal and/or Human Studies
Female Male• Effects on:
Oocyte & follicle development & function
Ovary formation, cell organization Uterine development Corpus luteum development &
function Pubertal development Menstrual & ovarian function
• Increased risk of: Cervical/vaginal cancer Infertility Miscarriage
• Effects on: Sertoli cell differentiation Spermatogonia formation, sperm
count Testis, prostate, penis development
• Increased risk of testicular germ cell cancer
• Low serum testosterone levels
Casarett and Doull’s Toxicology: The Basic Science of Poisons. 2007.
Environmental Effects Have Multiple Mechanisms
Examples:
Damage tooocytes/sperm
Interferencewith cell function
Changes to DNAstructure/gene expression
Toxicants
more…Casarett and Doull’s Toxicology: The Basic Science of Poisons. 2007.
Exposure May Affect DNA Structure and Gene Expression
Structural changesto DNA sequence
Functional changesto gene expression
more…
Casarett and Doull’s Toxicology: The Basic Science of Poisons. 2007.
Example:Hormone disruption
Modification ofgene expression
Chromosomal damage
Exposure May Affect DNA Structure and Gene Expression
Structural changesto DNA sequence
Functional changesto gene expression
Example:Gene mutations
Example:Birth defects and cancer
Examples:Altered hormone levels,early puberty, infertility
Casarett and Doull’s Toxicology: The Basic Science of Poisons. 2007.
Epigenetic Effects Result from Changes in Gene Expression
Epigenetic effects:• Not caused by internal changes in DNA• May be caused by external environmental factors
that modify gene activation• May be passed to subsequent generations
(preliminary evidence)
Bird A. Nature. 2007; Cavalli G, et al. Cell. 1998.
DES Cancer Network. 2008; Dieckman WJ, et al. Am J Obstet Gynecol. 1999; Herbst AL. N Engl J Med. 1971; NIEHS. 2008; Schrager S, et al. Am Fam Physician. 2004.
DES: An Example of Delayed Effects
• Given to pregnant women from 1930s to1970s to prevent miscarriage
• Linked to health effects in offspring
• Increased cancer risk; reproductive abnormalities
more…
DES Cancer Network. 2008; Dieckman WJ, et al. Am J Obstet Gynecol. 1999; Herbst AL. N Engl J Med. 1971; NIEHS. 2008; Schrager S, et al. Am Fam Physician. 2004.
DES: An Example of Delayed Effects (continued)
Examples of delayed effects in offspring:• High-risk pregnancy;
miscarriage• Increased vaginal, cervical,
breast cancer• Increased infertility• Structural defects in
reproductive organs
DES: An Example of Delayed Effects (continued)
Women who took DES while pregnant
DES Daughters DES SonsTestesPenis
ProstateEpididymis
FertilitySperm*
Seminal vesicles*
DESGranddaughters
MenstruationOvaries*Uterus*
DESGrandsons
PenisRete testis*
Seminal vesicles*Prostate*
DESGranddaughters
Ovaries*Uterus*
Immune system*
OvariesFallopian tubes
UterusCervix
VaginaBreastFertility
Pregnancy
Hormonal balanceMenopause
BonesImmune system
Adapted from Schwartz JM, Woodruff TJ. Shaping Our Legacy. 2008.
* = Effects in animals
Welshons WV. Environ Health Perspect. 2003.
Endocrine-Disrupting Chemicals
• Certain pesticides, industrial chemicals & byproducts, ingredients in plastics manufacture
--Interfere with hormonal levels or functions, including estrogen, testosterone, prolactin, LH, FSH, thyroid, etc.
--Demonstrated by rigorous animal studies & epidemiological observations
Position Statement on EDCs
Endocrine Society. 2009.
“Until such time as conclusive scientific evidence exists to either prove or disprove harmful effects of substances, a precautionary approach should be taken in the formulation of EDC policy.”
The Endocrine Society, June 2009
Woodruff TJ, et al. Fertil Steril. 2008; Harremoes P, et al. The Precautionary Principle in the 20th Century: Late Lessons from Early Warnings. 2002.
Lessons Learned from EDCs: PCBs
Name Polychlorinated biphenyls (PCBs)
UsesCoolants and lubricants in electrical equipment before 1977
Route of Exposure
Mainly food contamination; body burden levels had been decreasing but recently have leveled off
Woodruff TJ, et al. Fertil Steril. 2008.
EDC Lessons Learned: PCBs (continued)
Examples of potential effects:• Altered neurodevelopment as a result of in
utero exposure• Endometriosis• Reduced fertility• Decreased semen quality• Miscarriage• Altered pubertal development• Reproductive tract malformations
Assumption:Environmental
research indicates:
Doses below a certain threshold are safe.
Effects of very low doses have been underestimated.
High-dose testing predicts low-dose results.
High-level tests do not necessarily predict low-level impacts.
Effects typically increase with dose. Some effects are seen only at low levels.
Welshons WV, et al. Environ Health Perspect. 2003.
Conventional Assumptions Are Being Questioned
Andrade AJM, et al. Toxicology. 2006; Welshons WV, et al. Environ Health Perspect. 2003; Welshons WV, et al. Endocrinology. 2006.
Most Environmental Health Science Is Based on Animal Studies
• Most evidence derived from animal studies and epidemiologic observation (e.g., occupational studies)
• Effects found at “real-life” doses
Many Factors Complicate the Environmental Health Picture
• Epidemiological studies have limited capacity to identify causal relationships
• Many factors contribute to the complexity of observed health outcomes
• Clinical relevance of population exposures are not always clear in the individual
• “Safe” levels are often based on many factors that can influence the interpretation of the scientific data
“When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause-and-effect relationships are not fully established scientifically.”
Wingspread Consensus Statement on the Precautionary Principle. 1998.
“First, Do No Harm”
more…
Translating Population-Wide Risks into Individual Risks
• Clinicians work with individuals, not populations
• Elevated population-wide risks may represent a very small increased risk for an individual
Stoll C, et a. Arch Fr Pediatr. 1991; CDC. 2009.
Translating Population-Wide Risks into Individual Risks (continued)
• Modest increases in risk can result in major public health concerns if exposed population is large
• A large increase in population-wide risk will be increasingly important in individuals, even if not many people are exposed
• Two times a rare event = still a very rare event
Small Individual Effects Can Have Significant Population Effects
160140120100806040
IQ
Mean = 100
6.0 million:“gifted”
130
6.0 million:“mentallyretarded”
70Adapted from Weiss B. Neurotoxicology. 1997.
more…
Small Individual Effects Can Have Significant Population Effects (cont.)
IQAdapted from Weiss B. Neurotoxicology. 1997.
57% increase in
“mentally retarded” population
160140120100806040
Mean = 9560%
decrease in “gifted”
population
9.4 million:“mentallyretarded”
70
2.4 million:“gifted”
130
Relevant for Every Patient
• Assessment of exposure risk is relevant for all patients
• Particular focus on points of heightened susceptibility:▪ Preconception ▪ Pregnancy▪ Childhood▪ Pre-puberty▪ Adolescence
Community Home/Hobbies
Socioeconomic
Occupation/School
Personal
One Tool for Conducting an Environmental History: CH2OPS
CH2OPS: Community
Factories
Landfills
BusinessesHazardous waste
sites
Recreational areas
Farms
“So What Do I Do?”
• Learn about local environmental issues• Incorporate questions about exposures into every
health history• Suggest alternatives to reduce exposures• Give specific guidance to patients who may
become pregnant• Provide handouts and websites for patients • Conduct thyroid screening• Work with women to assess workplace exposures
The Environmental Health History
Environmental Health History Should Be Routine
HO
W?
WH
Y?
WHEN?
Vulnerable Stages: Early childhood Puberty Adolescence Preconception planning
(men & women) Pregnancy
Thyroid-Disrupting Chemicals
Blount BE, et al. Environ Health Perspect. 2006; Boas M, et al. Eur J Endocrinol. 2006; Longnecker MP, et al. Environ Health Perspect. 2003; Steinmaus C, et al. Environ Health Perspect. 2007; Boas M, et al. Eur J Endocrinol. 2006; Brucker-Davis F. Thyroid. 1998; DeVito M, et al. Environ Health Perspect. 1999 Miller MD, et al. Environ Health Perspect. 2009.
Hypothalamus
Pituitary
Hormone Synthesis
TRH
TSH
Thyroid XX
Iodine
Iodine uptake
XX
Free TH
Bound TH
T3 and T4
Blood
XX
Adapted from Miller MD. 2009.
Measuring Thyroid Function
Allan WC, et al. J Med Screen. 2000; Caturegli P, et al. Endocri Rev. 2005; Glinoer D. Trends Endocrinol Metab. 2998; Endocrine Society. 2007; Pearce EN. Thyroid. 2007; Dosiou C, et al. Eur J Endocrinol. 2008; Environ Health Perspect. 2006; Haddow JE. N Engl J Med. 1999. Image: Wikipedia. 2009.
Community: Guidance for Patients
Access community organizations & resources, for information about:• Dry cleaners that avoid toxic solvents• Salon products without toluene, phthalates, and
other toxic chemicals• Grocery stores that carry organic products
Resource Tip:• Download the What We Can Do: Community Efforts to Protect Our Health Tool Kit from the Women’s Health and the Environment Web site
CH2OPS: Home/Hobbies
• Pesticides• Adhesives• Furniture products• Cleaners• Detergents• Gardening products
(e.g., pesticides, plant food)
more…
CH2OPS: Home/Hobbies, cont.
Exposure to:• Carbon monoxide• Metals • Solvents
Fishing: • Be aware of fish advisories
for mercury
more…
Home: Guidance for Patients
• Check for lead paint and pipes; manage dust• Avoid canned foods and beverages• Avoid certain types of plastics:
▪ No. 3: Polyvinyl chloride (PVC)▪ No. 6: Styrene (Styrofoam)▪ No. 7: Polycarbonate (bisphenol A [BPA])
• Where possible, avoid food stored in plastic containers or plastic wrap
• Avoid vinyl products, such as shower curtain liners
Center for Health, Environment and Justice. 2008; NRDC. 2008; CDC. 2002.
Home: Guidance for Patients (continued)
• Use non-polycarbonate plastic or glass baby bottles
• Drink from unlined stainless steel bottles• Eat fresh food when possible
- frozen better than canned• Buy processed food in cardboard• Microwave food in glass or “microwave safe”
plastic containers
NRDC. 2008.
Home: Guidance for Patients (continued)
• Avoid using pesticides in homes, lawns, gardens, or on pets
• Wash fruits and vegetables; buy organic when possible; favor thick-skinned fruits and vegetables
Resource Tips:Extensive resources are available to eliminate the use of pesticides or to use less toxic
products. Some examples include:
• Visit www.beyondpesticides.org
• Visit the Pesticide Action Network (PAN): www.pesticideinfo.org
• Download the Shopper’s Guide to Pesticides wallet card from the Environmental Working Group
Home: Guidance for Patients (continued)
• Read labels on cleaning products • Use ammonia and chlorine bleach
sparingly, with ventilation• Avoid mixing ammonia and chlorine• Use inexpensive, nontoxic products
such as vinegar and baking soda
Resource Tip:• Find nontoxic cleaning recipes on the Women’s Voices for the Earth Web site or www.care2.com
Home: Guidance for Patients (continued)
FDA. 2009; EPA 1999; NRDC 2009.
Resource Tips:• Learn about local fish advisories from the EPA• Download a regional fish seafood-watch pocket guide from Seafood WATCH
Species to Avoid
Shark
Swordfish
King mackerel
Tilefish
Safer Choices
Trout
Salmon
Tilapia
Sardines
Hobbies: Guidance for Patients
• Understand mercury present in recreationally caught fish
• Use glue and solvents in well-ventilated spaces
• Garden with organic products
• Chemicals• Radiation• Biological agents• Pesticides in schools
CH2OPS: Occupation/School
Occupation: Guidance for Patients
• Become familiar with all chemicals used or encountered at work
• Learn about toxic properties of these chemicals• Wash any exposed skin; change from work clothes
at night; wash exposed clothes separately• Take extra care if pregnant (or planning pregnancy)• Use protective gear with toxic substances
or radiationResource Tip:• Learn more from the CDC report, “The Effects of Workplace Hazards on Female
Reproductive Health”
Occupation (Schools): Guidance for Patients
Advise patients:• Practice non-pesticide insect management; inform
parents if pesticides used• Use fruit &vegetables for snacks; avoid junk foods
in cafeterias• Avoid pressure-treated woods (arsenic) in
playground equipmentResource Tip:• Visit the Healthy Schools Network Web site and EPA’s Healthy School Environments
Web site to learn more about creating a healthier school environment
CH2OPS: Personal
• Dietary history • Alcohol use• Tobacco use• Prescription & non-
prescription medications• Substance abuse• Insect repellants• Cosmetics; personal
care products
Personal: Guidance for Patients
Advise patients: • Don’t trust “dermatologist-tested,” “natural,” “organic”• Learn about skin products that are safe for children• Avoid tobacco use; exposure to 2nd-hand smoke• Use alcohol in moderation
Resource Tips: • Check the safety of your own personal care products at the Skin Deep Cosmetic
Safety Database and the Campaign for Safe Cosmetics• Download the Safety Guide to Children's Personal Care Products from the
Environmental Working Group• Visit www.HealthyToys.org to find toy rankings and a safer toy shopping list
CH2OPS: Socioeconomic
• Living in higher levels of air pollution
• Exposure to lead, asbestos
• Limited access to nutritious food
• Vulnerability to other factors
Socioeconomic: Guidance for Patients
Advice for patients: • Know tenant & citizen rights • Work with community organizations, government
agencies to ensure risk awareness & knowledge
Resource Tip:• Visit the Alliance for Healthy Homes Web site for tools and tips on
reducing environmental hazards in homes and communities
Case Study: Jennifer
• 30 year old, married• Contemplating pregnancy in
next year• Lab technician at polymer
manufacturing company• Presents for annual well-
woman exam• Occasional headaches
What Questions Should You Ask?
• When do headaches occur?• Which chemicals?• What protection does she
use?
Material Safety Data Sheets
Material Safety Data Sheets. 2009.
Next Step?
• Order pregnancy test• Carefully explore her options for transferring
out of the lab to a less toxic work environment• Offer to write a letter to her employer with
recommendations for improved safety protections
• Consider an occupational health consult
Advocating for Workplace Safety
An Important Take-Home Message
Identifying and reducing exposures to potentially harmful toxicants now
increases the likelihood of a successful pregnancy outcome.
more…
Summary
• Environmental exposures have been linked to reproductive health effects and may affect future generations
• Exposures may have more significance at critical points:--Preconception --Pregnancy--Childhood--Pre-puberty--Adolescence
Summary (continued)
Clinicians can help by offering guidance, counseling, and resources:• Emphasize preconception care• Incorporate an environmental/occupational history
as part of patient health history• Be aware of risks in your community• Work with community groups to reduce
exposure levels • Provide education and information sources
ARHP Resources
Learn more at the ARHP Web site:• Click on Environmental and Reproductive Health
topic area • www.arhp.org/topics/enviro-repro-health
--Fact Sheet: Environmental and Reproductive Health Resources for Health Care Providers
--Patient handout: Health Matters: The Connection Between Your Health and the Environment
Resources for Clinicians
• Critical Windows of Development (www.endocrinedisruption.com): Online tool from The Endocrine Disruption Exchange (TEDX)
• ReproTox (www.reprotox.org): Summaries on the effects of >5,000 agents and exposures on pregnancy, reproduction, and development
• TOXNET (http://toxnet.nlm.nih.gov/): Databases on toxicology, hazardous chemicals, environmental health, and toxic releases
more…
Resources for Clinicians (continued)
• American College of Occupational and Environmental Medicine (www.acoem.org)
• Collaborative on Health and Environment (CHE) database (http://database.healthandenvironment.org/)
• EnviRN (www.envirn.umaryland.edu)• Local environmental health specialists• Occupational and environmental health
departments in universities
Visit CORE (www.arhp.org/core) to Download Slides